Anemia is a serious health issue for millions of people worldwide. The primary pharmacological treatment for anemia is recombinant erythropoietin ("EPO") injections, making it expensive and inconvenient and limiting its use in a large percentage of patients with anemia. Therefore, an orally-available small molecule EPO mimetic is expected to have economic and ease-of-use advantages. EPO activation of its receptor, EPOR, mediates a specific conformational change in the receptor that is referred to as dimerization. Importantly, EPO-mediated dimerization of EPOR is required for receptor activation. The pharmaceutical industry has not been very successful at identifying small molecule EPO mimetics despite considerable efforts to screen large combinatorial libraries using binding or functional assays. There is a clear need for alternative high throughput compound screening assays to identify small molecules capable of inducing EPO receptor dimerization. However, existing EPOR dimerization assays are not suitable for rapid screening of large chemical libraries. We propose to develop an assay to detect the conformational change associated with EPOR dimerization. We will use sensitive fluorescence-based approaches well suited for measuring protein conformational changes. The key technological advantage enabling us to develop a fluorescence-based dimerization assay is our novel approach for labeling of EPOR proteins which avoids substantial mutagenesis and non-specific labeling associated with existing protein labeling techniques. [unreadable] [unreadable] [unreadable]